Search Results (321)

Understanding the components of the diet, food groups, and nutritional strategies that help prevent MASLD (Metabolic Dysfunction-Associated Steatotic Liver Disease) is essential for identifying dietary behaviors that can stop the progression of this condition, which currently affects over one-quarter of the global population. This review highlights the importance of including antioxidant nutrients in the diet, such as vitamins C and E, CoQ10, and polyphenolic compounds. It also emphasizes substances that support lipid metabolism, including choline, alpha-lipoic acid, and berberine. Among food groups, it is crucial to choose those that help prevent metabolic disturbances. Among carbohydrate-rich foods, vegetables, fruits, and high-fiber products are recommended. For protein sources, eggs, fish, and white meat are preferred. Among fat sources, plant oils and fatty fish are advised due to their content of omega-3 and omega-6 fatty acids. Various dietary strategies aimed at preventing MASLD should include elements of the Mediterranean diet or be personalized to provide anti-inflammatory compounds and substances that inhibit fat accumulation in liver cells. Other recommended dietary models include the DASH diet, the flexitarian diet, intermittent fasting, and diets that limit fructose and simple sugars. Additionally, supplementing the diet with spirulina or chlorella, berberine, probiotics, or omega-3 fatty acids, as well as drinking several cups of coffee per day, may be beneficial. Full article

Photosynthesis in plants and the electron transport chain in mitochondria are examples of life-sustaining electron transfer processes. The benzoquinones plastoquinone and ubiquinone are key components of these pathways that cycle through their oxidized and reduced forms. Previously, we reported direct photoreduction of biologically relevant quinones mediated by photosensitizers, red light and electron donors. Herein we examined direct photoreduction of the quinone imine 2,6-dichlorophenolindophenol (DCPIP) using red light, methylene blue as the photosensitizer and ethylenediaminetetraacetic acid (EDTA) as the electron donor. Photoreduction of DCPIP by methylene blue and EDTA was very pH-dependent, with three-fold enhanced rates at pH 6.9 vs. pH 7.4. Photochemical redox cycling of DCPIP produced hydrogen peroxide via singlet oxygen-dependent reoxidation of reduced DCPIP. Histidine enhanced photoreduction by scavenging singlet oxygen, whereas increased molecular oxygen exposure slowed DCPIP photoreduction. Attempts to photoreduce DCPIP with pheophorbide A, a chlorophyll metabolite, and triethanolamine as the electron donor in 20% dimethylformamide were unsuccessful. Photoreduced benzoquinones including 2,3-dimethoxy-5-methyl-p-benzoquinone (CoQ₀), methoxy-benzoquinone and methyl-benzoquinone were used to examine electron transfer to DCPIP. For photoreduced CoQ₀ and methoxy-benzoquinone, electron transfer to DCPIP was rapid and complete, whereas for reduced methyl benzoquinone, it was incomplete due to differences in reduction potential. Nonetheless, electron transfer from photoreduced quinols to DCPIP is a rapid and sensitive method to investigate quinone photoreduction by chlorophyll metabolites. Full article

There is evidence for the involvement of mitochondrial dysfunction, oxidative stress, ferroptosis, and inflammation in the pathogenesis of obesity. This, in turn, indicates a novel potential therapeutic role for supplemental coenzyme Q10 (CoQ10) in the management of obesity, due to the role of CoQ10 in promoting normal mitochondrial function, as an antioxidant, and as an anti-ferroptotic and anti-inflammatory agent. In the present article we have, therefore, reviewed the potential role of CoQ10 in the prevention and treatment of obesity. A potential role for supplementary CoQ10 (in combination with selenium) in preserving skeletal muscle mass in obese individuals undergoing weight loss procedures is also discussed. Full article

Nitrogen-containing bisphosphonates (N-BPs) are commonly used drugs in the treatment of bone diseases due to their potent inhibition of the mevalonate pathway, leading to disrupted protein prenylation and reduced osteoclast activity. Although N-BPs are effective in reducing bone resorption, increasing evidence indicates their side effects on various non-skeletal cells. The aim of this review is to synthesize the current knowledge on the cellular and molecular effects of N-BPs outside the skeletal system, with particular emphasis on their impact on mitochondrial function and energy metabolism. At the cellular level, N-BPs may reduce viability, modulate inflammatory responses, trigger apoptosis, disrupt cytoskeletal organization, and influence signaling and energy metabolism. N-BPs may also impair the prenylation of proteins essential for mitochondrial dynamics and quality control, and may disrupt Ca²⁺ homeostasis. As we have shown in endothelial cells, by inhibiting the mevalonate pathway, N-BPs may lead to a reduction in key components of the mitochondrial respiratory chain, such as coenzyme Q (CoQ) and a-heme. These effects can contribute to impaired mitochondrial respiratory function, increased oxidative stress, and mitochondria-dependent apoptosis, affecting cellular energy metabolism and viability. These findings underscore the multifaceted impact of N-BPs beyond bone, emphasizing the importance of mitochondrial health and energy metabolism in understanding their broader biological effects and potential adverse outcomes. Full article

Coenzyme Q₁₀ (CoQ₁₀) has attracted widespread attention in recent years due to its momentous physiological functions. Microbial fermentation is the major method in CoQ₁₀ industrial production, and Rhodobacter sphaeroides is the main strain for the production of CoQ₁₀ by fermentation. Optimization of the culture medium is a popular solution to improve the metabolite production. Culture medium is the material basis for microbial growth and product synthesis, of which inorganic salts are a key ingredient. Uniform design (UD), artificial neural network (ANN), and genetic algorithm (GA) are the main research methods. Through uniform design (UD) and artificial neural network/genetic algorithm (ANN-GA) progressive optimization, an optimal formulation of the inorganic salts in fermentation medium was obtained (g·L⁻¹): MgSO₄ 12, NaCl 2.5, FeSO₄ 1.6, KH₂PO₄ 0.8, MnSO₄ 0.1, CaCl₂ 0.1. Ultimately, the fermentation yield of CoQ₁₀ could reach 255.36 mg·L⁻¹. ANN-GA exhibited a superior prediction capability compared to UD. Compared to UD, the optimization results of ANN-GA had a smaller relative error (ANN-GA 1.23%; UD 3.01%) and a higher increase rate in the fermentation level of CoQ₁₀ (ANN-GA 4.1%; UD 2.04%). R. sphaeroides had a high demand for Mg²⁺. Full article

The balanced control of the synthesis of CoQ along the life of the organism is essential to maintain the respiratory capacity at the mitochondria and the antioxidant protection of cell membranes and plasma lipoproteins. For this reason, we determined the levels of the transcripts of the CoQ-synthome along the life of mice in comparison with the levels of antioxidant enzymes and the levels of CoQ in these animals. Surprisingly, we found that some organs such as liver, kidney and heart show great differences in mRNA levels of some COQ-genes along life whereas others such as the brain or gastrocnemius muscle do not show differences. Interestingly, these differences were not related to the total amount of CoQ in these tissues, indicating a discrepancy between the transcript activity of the CoQ-synthome and the level of the product, CoQ. This likely responds to different regulatory levels including mRNA lifespan and CoQ turnover. Further, resveratrol and physical activity in old animals can modulate some transcripts but many of them are in an organ-dependent effect, indicating a different response to the regulators. Full article

Objectives: The aim of this study was to evaluate the impact of a novel antioxidant formulation (RE:PAIR, RP-25) containing CoQ10, alpha-lipoic acid, and Chaga extract on mitochondrial dysfunction and oxidative stress. To explore the activity of the formulation on neuronal cells, we explored cell metabolism and its activity as an antioxidant, using a combination of NMR-based metabolomics and UHPLC-HRMS analytical techniques. Methods: SH-SY5Y neuroblastoma cells were treated with RP-25, and cell viability was assessed via CCK-8 assay. Metabolomic profiles of the treated and untreated cells were analyzed by 1D-NMR, providing insights into both intracellular metabolites (endometabolome) and excreted metabolites (exometabolome). Additionally, a UHPLC-HRMS method was developed for quality control and analysis of the RP-25 formulation. Multivariate statistical approaches, including PLS-DA and volcano plot analyses, were used to identify key metabolic changes. Changes in mitochondrial membrane potential were assessed by means of TMRE assay, while radical oxygen species (ROS) were measured by means of the DCHF assay. Results: RP-25 treatment did not affect cell viability but significantly increased metabolic pathways, including amino acid biosynthesis, oxidative phosphorylation, and glycolysis. Higher levels of ATP, glutamate, tyrosine, and proline were observed in treated cells than in control cells, indicating enhanced cellular energy production, as also proved by the increased stability of the mitochondrial membrane after RP-25 treatment, an index of preserved mitochondrial functions. In support, the formulation RP-25 showed antioxidant activity when cells underwent peroxide oxygen stimulation. This effect was mainly due to the combination of Chaga, CoQ10, and ALA, main components of the RP25 formulation. Moreover, the analysis of enriched pathways highlighted that RP formulation influenced mitochondrial energy and oxidative stress response. Conclusions: RP-25 demonstrated biological activity in that it mitigated mitochondrial dysfunction and oxidative stress in neuronal cells, with potential implications in neuronal diseases associated with dysfunctional mitochondria. Full article

Mitochondria are primary targets for environmental toxic chemicals; these typically disrupt the mitochondrial electron transport chain, resulting in reduced ATP production, increased reactive oxygen free radical species (ROS)-induced oxidative stress, increased apoptosis, and increased inflammation. This in turn suggests a rationale for investigating the potential role of coenzyme Q10 (CoQ10) in mediating such chemical-induced mitochondrial dysfunction, given the key roles of CoQ10 in promoting normal mitochondrial function, and as an antioxidant and anti-apoptotic and anti-inflammatory agent. In the present article, we have, therefore, reviewed the potential role of supplementary CoQ10 in improving mitochondrial function and mediating adverse effects following exposure to a number of environmental toxins, including pesticides, heavy metals, industrial solvents, endocrine-disrupting agents, and carcinogens, as well as pharmacological drugs and lifestyle toxicants. Full article

AarF domain-containing kinases (ADCKs) are a family of putative mitochondrial proteins that have been implicated in various aspects of mitochondrial function and cellular metabolism. Mitochondria play a crucial role in cellular bioenergetics, primarily in adenosine triphosphate (ATP) production, while also regulating metabolism, thermogenesis, apoptosis, and reactive oxygen species (ROS) generation. Evidence suggests that the ADCK family of proteins is involved in maintaining mitochondrial architecture and homeostasis. In detail, these proteins are believed to play a role in processes such as coenzyme Q biosynthesis, energy production, and cellular metabolism. There are five known isoforms of ADCK (ADCK1–ADCK5), some of which have similar activities, and each also has its own unique biological functions. Dysregulation or mutations in specific ADCK isoforms have been linked to several pathological conditions, including multiple human cancers, primary coenzyme Q10 (CoQ10) deficiency, and metabolic disorders. This review surveys the current body of peer-reviewed research on the ADCK protein family, incorporating data from the primary literature, case studies, and experimental studies conducted in both in vitro and in vivo systems. It also draws on existing review articles and known published findings to provide a comprehensive overview of the functional roles, disease associations, and molecular mechanisms of ADCK proteins. Further in-depth research on ADCK proteins has the potential to unlock critical insights into their precise mechanisms. This could pave the way for identifying new therapeutic targets for mitochondrial and metabolic-related diseases, as well as for advancing cancer treatment strategies. Full article

Background: Low selenium intake and age-related decline of coenzyme Q₁₀ (CoQ₁₀) have been associated with an increased risk of cardiovascular disease (CVD) and oxidative stress. In a randomised placebo-controlled trial (RTC) in elderly people with low selenium levels, the supplementation with selenium and CoQ₁₀ reduced CVD and mortality. However, whether the supplementation elicited sex-specific benefits remained to be explored. Methods: Elderly Swedish persons (n = 443; balanced sex ratio) receiving selenium yeast (200 µg/day) and CoQ₁₀ (200 mg/day) combined or a placebo for four years were followed for additional six years. The response to supplementation, cardiovascular (CV) mortality, and risk factors were determined at four and ten years. Kaplan–Meier analyses, ANCOVA, repeated measurements of variance, and Cox proportional hazard regression analyses were performed. Results: The measured 10-year CV mortality rate was lower in females, and supplementation reduced this risk to a greater extent compared to in males. The improved survival rate apparently kicked in later in females than in males. At baseline, males had a higher smoking rate, increased inflammation and oxidative stress, and a higher prevalence of more advanced ischaemic heart disease (IHD) and signs of heart failure. When stratified by sex, in individuals with IHD, the intervention improved CV survival in both sexes, whereas supplementation had a more pronounced effect in females without IHD at inclusion. Supplementation diminished inflammation and oxidative stress, impaired the increase of NT-proBNP, and improved renal function in both sexes. Conclusions: The supplementation improved CV survival, especially in women. The higher prevalence of structural CVD and smoking in males may have contributed to the observed greater supplementation benefits in females. The preventive impact of selenium and CoQ₁₀ supplementation in elderly males and females may be particularly strong and meaningful in the early stages of CVD development. Full article

The incidence of morbidity and mortality in patients who have suffered traumatic brain injury (TBI) is such that novel therapeutic strategies are currently required. There is good evidence that ischaemia is the primary, and sometimes the secondary, cause of brain damage in TBI. This ischaemia may lead to mitochondrial dysfunction, with associated oxidative stress and inflammation, in the pathogenesis of brain injury following head trauma. This, in turn, provides a rationale for the use of supplemental coenzyme Q10 (CoQ10) in the management of TBI, given its key roles in normal mitochondrial function and as an antioxidant and anti-inflammatory agent. In this article, we, therefore, review the use of supplemental CoQ10 in animal models of TBI and its potential application in the management of TBI patients. The problem of blood–brain barrier access is discussed, and how this might be circumvented via the use of an intranasal route to provide direct access of CoQ10 to the brain. In addition, there is evidence that TBI patients have an increased risk of developing cardiac dysfunction and that this may be mediated by aberrant immune action. Given the role of CoQ10 in promoting normal cardiac function and normal immune function, the administration of CoQ10 to prevent cardiovascular complications may improve outcomes in TBI patients. Full article

Background/Objectives: Heart failure remains a complex syndrome with high morbidity and mortality, highlighting the urgent need for alternative treatments that address underlying bioenergetic impairments. CoQ10, which plays a crucial role in mitochondrial ATP production, has shown promising results in small studies, although larger trials are needed to confirm its efficacy. Results: This randomized controlled trial investigated the effects of coenzyme Q10 (CoQ10) supplementation on cardiac function and quality of life in heart failure patients. A total of 120 patients were randomly assigned to receive either CoQ10 (2 × 60 mg daily) or a placebo for six months. Baseline characteristics were similar between groups. The primary outcomes were changes in global longitudinal strain (GLS) and left ventricular ejection fractions (LVEFs), while secondary outcomes included improvements in functional capacity and quality of life. At the 6-month endpoint, the CoQ10 group showed significant improvements in GLS (−11.7% to −14.9%, p < 0.001), NT-proBNP levels (815.6 vs. 1378.5 pg/mL, p = 0.012), blood pressure, and 6 min walk test distance (349.3 vs. 267.0 m, p = 0.008) compared to the placebo group. LVEFs improved slightly in the CoQ10 group (38.9% to 40.6%, p = 0.170) but remained unchanged in the placebo group. Conclusions: These findings suggest that CoQ10 supplementation may improve cardiac function, reduce cardiac stress, and enhance functional capacity and quality of life in heart failure patients. Further research is needed to optimize dosage and identify the subgroups that may benefit most from CoQ10 therapy. Full article

Coenzyme Q10 is a natural antioxidant with anti-tumor and mitochondrial protective effects. However, its unstable physicochemical properties and large molecular weight result in low bioavailability. This study aimed to develop an effective technique for constructing nanoliposomes to improve the physicochemical properties of CoQ10 by using high-pressure microfluidic homogenization. Liposomes were prepared using the ethanol injection method and homogenized by high-pressure microfluidics to optimize their physicochemical properties. Liposome morphology and microstructure were observed via transmission electron microscopy (TEM). The particle size distribution, polydispersity index (PDI), and encapsulation efficiency were assessed, while effects on cell viability and antioxidant properties were investigated in HepG2 cells. The results indicate that the prepared liposomes exhibit favorable characteristics, including high encapsulation efficiency (>96%) and low PDI (<0.3), indicating uniform particle size distribution and good stability. The storage stability of liposomes at room temperature was significantly enhanced compared to liposomes not subjected to high pressure homogenization. In vitro cell experiments confirmed the liposomes’ non-cytotoxicity and substantial antioxidant activity, ensuring their safety for biomedical applications. This study introduced a liposome preparation method combining ethanol injection and high-pressure microfluidic homogenization, offering a novel approach for liposome modification with potential for development and application in innovative drug delivery systems and antioxidant therapy. Full article

Mitochondria possess a double-membrane envelope which is susceptible to insult by pathogenic intracellular aggregates of amyloid-forming peptides, such as the amyloid-beta (1-42) (Aβ42) peptide and the human islet amyloid polypeptide (hIAPP). The molecular composition of membranes plays a pivotal role in regulating peptide aggregation and cytotoxicity. Therefore, we hypothesized that modifying the physicochemical properties of mitochondrial model membranes with a small molecule might act as a countermeasure against the formation of, and damage by, membrane-active amyloid peptides. To investigate this, we inserted the natural ubiquinone Coenzyme Q10 (CoQ10) in model mito-mimetic lipid vesicles, and studied how they interacted with Aβ42 and hIAPP peptide monomers and oligomers. Our results demonstrate that the membrane incorporation of CoQ10 significantly attenuated fibrillization of the peptides, whilst also making the membranes more resilient against peptide-induced permeabilization. Furthermore, these protective effects were linked with the ability of CoQ10 to enhance membrane packing in the inner acyl chain region, which increased the mechanical stability of the vesicle membranes. Based on our collective observations, we propose that mitochondrial resilience against toxic biomolecules implicit in protein misfolding disorders such as Alzheimer’s disease and type-2 diabetes, could potentially be enhanced by increasing CoQ10 levels within mitochondria. Full article

Background/Objectives: The loss of retinal ganglion cells (RGCs) is a hallmark of glaucoma, a major cause of blindness. Glial cell activation due to increased intraocular pressure (IOP) significantly contributes to RGC death. Therefore, substances with anti-inflammatory properties could help prevent that process. This study investigated whether combining Citicoline and Coenzyme Q10 (CoQ10) can reduce glial activation in the retina and the rest of the visual pathway, potentially preventing neurodegeneration in a mouse model of unilateral laser-induced ocular hypertension (OHT). Methods: Four groups of mice were used: vehicle (n = 12), CitiQ10 (n = 12), OHT–vehicle (n = 18), and OHT–CitiQ10 (n = 18). The administration of Citicoline and CoQ10 was performed orally once a day, initiated 15 days prior to the laser treatment and maintained post-treatment until sacrifice (3 days for retina or 7 days for the rest of the visual pathway). The retina, dorsolateral geniculate nucleus, superior colliculus, and visual cortex (V1) were immunohistochemically stained and analyzed. Results: In the laser–CitiQ10 group, the Citicoline + CoQ10 compound revealed (1) an IOP decrease at 24 h and 3 days post-laser; and (2) reduced signs of macroglial (decreased GFAP area) and microglial (soma size, arbor area, microglia number, P2RY12 expression) activation in the retina and in the rest of the visual pathway (reduced activated microglial phenotypes and lower GFAP expression). Conclusions: This study shows that oral administration of Citicoline and CoQ10 can reduce glial activation caused by increased IOP in retina and visual pathway in a mouse model of OHT, potentially protecting RGCs from OHT-induced inflammation. Full article